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In vitro studies of 3-hydroxy-4-pyridinones and their glycosylated derivatives as potential agents for Alzheimer’s disease.

TitleIn vitro studies of 3-hydroxy-4-pyridinones and their glycosylated derivatives as potential agents for Alzheimer’s disease.
Publication TypeJournal Article
Year of Publication2010
AuthorsGreen, DE, Bowen, ML, Scott, LE, Storr, T, Merkel, M, Boehmerle, K, Thompson, KH, Patrick, BO, Schugar, HJ, Orvig, C
JournalDalton Transactions
Volume39
Pagination1604 - 1615
Date Published2010///
ISBN Number1477-9226
Keywordshydroxypyridinone Alzheimers disease
Abstract

Glycosides of 3-hydroxy-4-pyridinones were synthesized and characterized by mass spectrometry, elemental anal., 1H and 13C NMR spectroscopy, and in one case by X-ray crystallog. The Cu2+ complex of a novel 3-hydroxy-4-pyridinone was synthesized and characterized by IR and X-ray crystallog., showing the ability of these compds. to chelate potentially toxic metal ions. An MTT cytotoxicity assay of a selected glycosylated compd. showed a relatively low toxicity of IC50 = 570 ± 90 μM in a human breast cancer cell line. The pyridinone glycosides could be cleaved by a broad specificity beta-glycosidase, Agrobacterium sp.β-glucosidase, and for one compd. kcat and Km were detd. to be 19.8 s-1 and 1.52 mM, resp. Trolox Equiv. Antioxidant Capacity (TEAC) values were detd. for the free pyridinones, indicating the good antioxidant properties of these compds. Metal-Aβ1-40 aggregates with zinc and copper were resolubilized by the non-glycosylated pyridinone ligands. [on SciFinder(R)]